中成药2025，Vol.47Issue(6)：1843-1852,10.DOI:10.3969/j.issn.1001-1528.2025.06.010
基于PI3K/Akt/mTOR信号通路探讨解毒益智方对阿尔茨海默病小鼠神经炎症的影响
Effects of Jiedu Yizhi Formula on neuroinflammation in a mouse model of Alzheimer's disease via PI3K/Akt/mTOR signaling pathway
摘要
Abstract
AIM To investigate the mechanism of Jiedu Yizhi Formula on cognitive function and neuroinflammation in a mouse model of Alzheimer's disease(AD).METHODS 50 APP/PS1 double transgenic mice were randomly divided into the model group,the donepezil group,and the low-dose,moderate-dose,and high-dose Jiedu Yizhi Formula group(1.78,3.56 and 7.12 g/kg),with 10 mice in each group,in contrast to the 10 WT mice of the blank group.Following anesthesia administration and 8-week oral gavage regimen with respective drugs,all mice underwent final tissue sample collection.The mice had their learning and memory ability assessed by Morris water maze and nesting behavior scores;their pathology of brain tissue and Aβ expression observed using HE,Nissl and IHC staining;their polarization of microglia and the expression of inflammatory factors in hippocampal tissue detected by IF and ELISA;their hippocampal expression of PI3K/Akt/mTOR signaling pathway detected by RT-qPCR and Western blot.RESULTS Compared with the blank group,the model group had lower scores in total swimming distance,frequency in crossing the platform,residence time in the target quadrant,and nesting behavior scores(P＜0.05,P＜0.01);prolonged evasion latency(P＜0.01);more disorganized arrangement of pyramidal cells,solidification and deep staining,unclear demarcation,irregular cell shapes,reduction of Nyctinidia,and increased Aβ deposition in the brain tissue(P＜0.01);elevated expression of hippocampal microglia M1-type markers CD16/32 and lba-1(P＜0.01);decreased levels of M2-type marker CD206(P＜0.05);elevated levels of TNF-α and IL-1β(P＜0.01);decreased expressions of IL-13 and IL-4(P＜0.01);and decreased levels of PI3K,Akt and mTOR mRNA,and reduced p-PI3K,p-Akt and p-mTOR protein expressions(P＜0.01).Compared to the model group,the donepezil group and the Jiedu Yizhi Formula groups showed statistically significant improvements in the aforementioned indexes(P＜0.05,P＜0.01),with the magnitude of improvement being higher in the high-dose Jiedu Yizhi Formula group.CONCLUSION Jiedu Yizhi Formula suppresses microglia Ml-type polarization while enhancing M2-type polarization via activation the PI3K/Akt/mTOR signaling pathway,which subsequently reduces inflammatory cytokine secretion.This mechanism attenuates Aβ deposition in brain tissues and ameliorates cognitive dysfunction in AD mouse models.关键词
解毒益智方/阿尔茨海默病/小胶质细胞/Aβ沉积/神经炎症/PI3K/Akt/mTOR信号通路Key words
Jiedu Yizhi Formula/Alzheimer's disease/microglia/Aβ deposition/neuroinflammation/PI3K/Akt/mTOR signaling pathway分类
中医学引用本文复制引用
王杰,刘健,朱晓婷,李云强,张馨月,李凡,吴佳丽,李威,黎明全..基于PI3K/Akt/mTOR信号通路探讨解毒益智方对阿尔茨海默病小鼠神经炎症的影响[J].中成药,2025,47(6):1843-1852,10.基金项目
吉林省自然科学基金(YDZJ202201ZYTS232) （YDZJ202201ZYTS232）
